Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors (NCT03693846), a na phase 2 study. The primary outcome is Number of Participants With Progression-Free Survival at 6 Months.

2. Clinical Question

In practical statistical terms, the study was designed to describe the 6-month progression-free status of participants receiving the combination, rather than estimate a difference between the combination and a separate treatment or control. The disease setting and prior-treatment history define the group to which the registry summary refers; the record does not provide further detail about eligibility criteria or the characteristics of enrolled participants.

The study is identified as NCT03693846 and is listed as phase II. Its brief summary describes a plan for twenty-one subjects, while the recorded enrollment is 11. That distinction matters when interpreting the precision of any group-level result: the planned count and the enrolled count are not interchangeable. Because the primary endpoint result is not reported in the registry record, the posted information does not establish the observed 6-month progression-free count or its uncertainty.

3. Trial Design

NCT03693846 is a phase II, single-group study of nivolumab and ipilimumab in mucinous colorectal and appendiceal tumors. The record lists Abramson Cancer Center at Penn Medicine as the sponsor. It gives a start date of 2019-02-15 and a primary completion date of 2021-03-06, and its current status is terminated. The reason for termination is not reported in the registry record.

The treatment group received nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks. The treatment description states that therapy continued until disease progression, unacceptable toxicity, withdrawal of consent, or 24 months of therapy. The brief summary describes participants with mucinous adenocarcinoma of the colon, rectum, or appendix after prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan. Further details of eligibility and treatment delivery are not reported in the registry record.

The design is single-group, with no masking and no randomized allocation. There is consequently no concurrent control arm in the record against which to estimate a comparative treatment effect. Findings from this design can describe the enrolled group and its recorded outcomes, but cannot by themselves separate treatment effects from the course of disease, participant selection, or other influences.

The brief summary gives a planned enrollment of twenty-one subjects; recorded enrollment is 11. The reason for the difference is not reported in the registry record. The record lists secondary outcomes of progression-free survival, overall survival, objective response rate, and duration of response. It also lists five outcome measures, but no analysis entries. A formal statistical plan, sample-size justification, interim-analysis plan, and reason for termination are not reported in the registry record. The record does not identify a separate comparator or report that randomization took place.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Eleven subjects were consented/enrolled and active on study treatment for at least one cycle.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Progression-Free Survival at 6 Months, measured over Start of treatment until 6 months later.

The primary endpoint is the number of participants with progression-free survival at 6 months. Its timeframe is the start of treatment until 6 months later, and the description specifies assessment by iRECIST. The endpoint is expressed as a count of participants, rather than as a time-to-event estimate or a difference between groups.

Progression-free survival generally describes the period during which disease has not progressed; in this registry outcome, the relevant question is whether participants meet the progression-free criterion at the specified 6-month assessment. As a general statistical concept, a fixed-time endpoint can give a clinically interpretable snapshot at a prespecified point. It does not, on its own, show when progression occurred for participants who did not meet the endpoint, or how long participants remained progression-free beyond that point.

The endpoint is useful for describing the outcome in the treated group, but its interpretation depends on the recorded assessment rules, follow-up, and handling of missing status. Those details are not reported in the registry record. The number of participants meeting the endpoint, the denominator used for the result, and any uncertainty interval are also not reported in the registry record. Therefore, the endpoint definition can be described, but the observed 6-month outcome cannot be reconstructed from the posted information.

iRECIST is named as the assessment approach in the primary outcome description. The record does not provide further detail about assessment procedures or adjudication. The endpoint should not be confused with the listed secondary outcomes, which include overall survival, objective response rate, duration of response, and progression-free survival. Their definitions and results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the study structure. This is a single-group phase II study, not a randomized comparison. The registry lists allocation as not applicable and masking as none. In general, randomization helps balance known and unknown prognostic factors between comparison groups, while masking can reduce some forms of measurement or decision bias. Neither feature creates a control group in this record. Outcomes describe the enrolled group receiving the combination, but the design does not estimate a between-group treatment contrast.

What does the primary count represent?

The primary measure is a count: participants with progression-free survival at 6 months from treatment start, using iRECIST. A count is meaningful only alongside its denominator and the rule used to determine whether each participant meets the endpoint. The registry description gives the endpoint and timeframe, but the result count, analysis denominator, and missing-status handling are not reported in the registry record. It is therefore not possible to turn the endpoint definition into an observed proportion or to assess its precision from the registry record.

As a general concept, a confidence interval describes the range of values reasonably compatible with the observed data under a specified statistical model. Its width reflects both the amount of information and variability. A point estimate without an uncertainty interval may look more definite than the data warrant. No confidence interval for the primary endpoint is reported in the registry record, and none can be inferred from the endpoint description alone.

Why does the single-group structure matter?

A single-group outcome can be compared with an external expectation only if that expectation and the comparison method are specified and justified. Neither an external comparator nor such a comparison is reported in the registry record. A change over time within participants would also require suitable repeated measurements and an analysis plan; those details are not reported. General statistical caution is warranted because differences in patient mix, follow-up, assessment, and calendar context can make comparisons across separate studies unreliable.

The record gives enrollment as 11 and the brief summary describes a plan for twenty-one subjects. This is relevant to the amount of information available, but it does not itself determine whether any estimate is statistically significant or clinically important. The endpoint result and its uncertainty are absent. The rationale behind the planned enrollment, assumptions about the expected endpoint, and any formal power calculation for the trial are not reported in the registry record.

How should planning calculations be understood?

The posted planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a stated fraction of the observed effect. Those are illustration settings, not evidence that this trial had two arms: the actual registry design is single-group. The illustration is also not the trial’s own sample-size justification. Its calculated sample sizes are planning illustrations, not observed power. The record does not report a protocol-based justification for the planned enrollment or explain how any illustrative assumptions relate to the study design.

In general, power is a design-stage probability concerning detection of a specified effect under specified assumptions. It is not a property that can be established by taking the observed result and calculating a retrospective “observed power.” For a completed study, estimates and confidence intervals are more informative descriptions of what the data support. Here, the primary endpoint result and uncertainty interval are not reported in the registry record, so neither can be interpreted from the posted information.

What are analysis entries and outcome measures?

The registry lists five outcome measures and no analysis entries. An outcome measure describes what is intended to be assessed; an analysis entry would provide additional statistical detail or a reported analysis. The absence of analysis entries means that analytic methods such as model choice, adjustment variables, censoring rules, or subgroup procedures are not reported in the registry record. It does not establish that no analyses were performed outside the registry.

The secondary outcomes include progression-free survival, overall survival, objective response rate, and duration of response. These outcomes address distinct questions. As general concepts, time-to-event outcomes account for the timing of an event and may require methods for censoring; response measures require defined criteria and an analysis population; duration of response applies to participants who meet a response definition. The registry record does not report the operational definitions, estimates, uncertainty, or analysis populations for these secondary outcomes.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular amount of variation. Over-dispersion means the observed variation is greater than that assumed by a model, which can make standard errors too small and confidence intervals too narrow if it is ignored. This is a general statistical issue, not a reported feature of this study. The primary endpoint is recorded as a participant count, but the registry record does not report a model or dispersion estimate. It would be inappropriate to claim that over-dispersion was present or that any particular correction was used.

Overall, the record allows a description of the design, treatment schedule, endpoint definition, enrollment, and selected adverse-event counts. It does not provide enough statistical results to judge the magnitude or precision of the primary outcome, the secondary outcomes, or a treatment effect relative to a comparator.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Nivolumab and Ipilimumab")
n      <- c(11)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Nivolumab and Ipilimumab  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are assessed. In general, the more tests conducted, the greater the chance that at least one result appears noteworthy by chance unless the analysis plan addresses that issue. The record lists a primary outcome and secondary outcomes of progression-free survival, overall survival, objective response rate, and duration of response. It does not report whether or how multiplicity was handled. The prespecified testing hierarchy, any adjustment method, and any distinction between confirmatory and exploratory analyses are not reported in the registry record.

Missing data can affect a fixed-time endpoint if a participant’s status at the assessment point is unknown. As a general concept, results can depend on whether participants with missing status are excluded, counted as not meeting the endpoint, or handled with another method. The primary outcome description does not specify missing-data rules, and those rules are not reported in the registry record. The endpoint denominator and amount of missing outcome information are also not reported.

Analysis populations are the defined groups of participants included in an analysis, such as all enrolled participants or participants meeting particular criteria. The registry record does not describe the primary or secondary analysis populations. It also does not report whether participants who stopped treatment, withdrew consent, or had incomplete follow-up remained in outcome analyses.

These omissions limit reproducibility and interpretation. They do not establish that multiplicity, missingness, or analysis populations were mishandled; they mean the relevant methods are not reported in the registry record. No statistical plan, interim-analysis plan, or rules for outcome adjudication are reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small intestine obstruction (18.2%), atrial fibrillation (18.2%), small intestine perforation (9.1%), myocarditis (9.1%), colonic obstruction (9.1%).

The safety record lists 11 participants at risk for other adverse events and 11 with other adverse events. For serious adverse events, 11 participants were at risk and 9 were affected. These are participant counts; they do not show how many total episodes occurred, how long participants were followed, or the severity distribution beyond the serious-event classification.

The listed serious-event terms include Small Intestine Obstruction and Atrial fibrillation, each reported as 18.2%. Small Intestine Perforation, Myocarditis, Colonic Obstruction, and Thromboembolic Event are each reported as 9.1%. These percentages describe the terms as listed in the registry. The record does not provide event-level detail, timing, recurrence, or information about whether events were considered related to treatment.

The group lists 5 deaths. The registry figures do not establish the causes of those deaths or whether they were treatment-related. Serious adverse events, other adverse events, and deaths are distinct measures; they should not be combined or treated as interchangeable. The record does not report further detail about follow-up duration or the methods used to collect and classify safety events.

As a general statistical caution, safety counts from a single small group are descriptive. They do not provide a controlled estimate of excess risk, and a percentage does not by itself establish causation. The available counts should therefore be read as recorded events among participants in this group, not as proof that nivolumab, ipilimumab, or their combination caused any particular event.

13. What the Result Does, and Does Not, Mean

The registry record establishes that this was a phase II, single-group study of nivolumab and ipilimumab in mucinous colorectal and appendiceal tumors, with a primary endpoint defined as the number of participants with progression-free survival at 6 months by iRECIST. It also records enrollment of 11, a terminated status, and selected safety counts. These registry entries describe the study and what its registry record contains.

The record does not report the primary endpoint result. It therefore does not show how many participants met the 6-month progression-free survival definition, how precise an estimate would be, or how the observed result compared with a prespecified target. It also does not report results for the listed secondary outcomes. A missing registry result is not equivalent to a result of zero, and it does not establish that the study found no effect.

Because there is no randomized comparator, the design cannot isolate a treatment effect from other explanations for an observed outcome. Even if outcome results were available, descriptive findings in a single group would not provide the same evidence as a controlled comparison. The posted information does not establish that the treatment combination improves, worsens, or has no effect on any clinical outcome.

The adverse-event counts identify participants with events and list selected serious event terms. They do not by themselves establish causality, comparative safety, or the risk that would be observed in a different population. The record also does not state why the study was terminated. That status should not be taken as evidence of a particular efficacy or safety conclusion.

In short, the design and endpoint can be described, as can the recorded enrollment and safety figures. The clinical outcome estimates needed to assess the primary question are not reported in the registry record. This absence limits interpretation; it should not be replaced with assumptions about unreported analyses or outcomes.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an outcome definition and an outcome result. A registry can specify a clear question—here, the number of participants with progression-free survival at 6 months by iRECIST—without reporting the observed count or its uncertainty. Readers need both the definition and results to assess what the study found.

The single-group structure also illustrates why design determines the kind of inference that is available. The recorded experience of participants receiving nivolumab and ipilimumab can be described, but the study does not include a concurrent control group for a direct comparison. A treatment comparison cannot be recovered simply by interpreting a group’s outcome in isolation.

The difference between the planned enrollment of twenty-one subjects in the brief summary and recorded enrollment of 11 highlights why actual enrollment should be distinguished from planning targets. Enrollment affects the amount of information that might be available, but it does not reveal the endpoint result, its precision, or the reason the study ended. Those elements require reported outcomes and analysis details.

Finally, the record lists safety counts alongside an absent primary outcome result. That makes it important to keep descriptive safety data separate from efficacy conclusions. The serious-event terms and participant counts are useful features of the registry record, but they do not substitute for a controlled safety comparison or establish causality. The study’s statistical importance lies in reading these data within the limits of the design and the reported information, rather than treating an endpoint definition or a registry status as a result.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting clinical outcomes is that the primary endpoint result is not reported in the registry record. The count of participants meeting the 6-month progression-free survival definition, the analysis denominator, and an uncertainty estimate are absent. Results for the listed secondary outcomes are also not reported in the registry record. Consequently, the posted information does not support an estimate of the magnitude or precision of the primary outcome.

The design is single-group, with no randomized allocation, masking, or control arm. This prevents a like-for-like comparison and limits causal interpretation. The record describes prior systemic therapy with a fluoropyrimidine, oxaliplatin, and irinotecan, but does not report enough participant characteristics to assess how representative the enrolled group may be. Additional eligibility and baseline details are not reported in the registry record.

Recorded enrollment is 11, while the brief summary describes a plan for twenty-one subjects. The reason for the difference is not reported in the registry record. The status is terminated, but its reason is also not reported. The registry does not provide the trial’s sample-size justification, analysis plan, interim-analysis plan, multiplicity approach, missing-data rules, or analysis populations.

Safety information is limited to participant counts and selected serious-event terms and percentages. Event timing, duration, recurrence, attribution, and cause of death are not reported in the registry record. These limitations do not imply that the study’s conduct or analysis was inadequate; they define what can be interpreted from the posted registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nivolumab and Ipilimumab in Mucinous Colorectal and Appendiceal Tumors — NCT03693846.
• Registry record last updated 2022-10-20; status last verified 2022-09.
• Results first posted 2022-10-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03693846 is a phase II, single-group study of nivolumab and ipilimumab in mucinous colorectal and appendiceal tumors, sponsored by Abramson Cancer Center at Penn Medicine. The record lists a start date of 2019-02-15, a primary completion date of 2021-03-06, and a terminated status. The reason for termination is not reported in the registry record.

The treatment schedule was nivolumab 480mg every 4 weeks and ipilimumab 1mg/kg every 8 weeks. The primary endpoint was the number of participants with progression-free survival at 6 months by iRECIST. Planned enrollment in the brief summary was twenty-one subjects; recorded enrollment was 11. The primary and secondary outcome results are not reported in the registry record.

The safety record reports 9 of 11 participants with serious adverse events, 11 of 11 with other adverse events, and 5 deaths. Selected serious-event terms are listed with percentages. These descriptive data do not establish treatment causation or a comparative risk.